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Biomedical subjects

C Landau

Publications and source records attributed to C Landau.

53 records · Page 3Linked to original sources

Microwave balloon angioplasty effectively seals arterial dissections in an atherosclerotic rabbit model.

OBJECTIVES: The purpose of this study was to determine the effectiveness of microwave balloon angioplasty in sealing arterial dissections and to characterize the histologic features associated with this intervention. BACKGROUND: Coronary dissection accompanying balloon dilation is frequently associated with abrupt closure and acute ischemic complications. Effective management of this complication remains an active area of investigation. Because thermal energy is effective in welding separated atherosclerotic plaques, a microwave-based catheter system that provides controlled local heating was utilized in vessels with angioplasty-induced dissections. METHODS: Iliac artery dissections were induced in ahypercholesterolemic rabbit model. Vessels were randomly assigned to treatment with standard balloon angioplasty (control vessels) or microwave balloon angioplasty using an average temperature of 80 degrees C. The response of the artery was assessed angiographically and histologically. RESULTS: Angiographic success, defined as a reduction of dissection length by > 50% or the resolution of lumen haziness, was achieved in 63% of microwave-treated vessels and in 16% of control vessels (p < 0.005). Dissection length (mean +/- SD) was reduced 8.0 +/- 4.8 mm in microwave-treated vessels compared with 0.1 +/- 7.9 mm in vessels receiving standard balloon inflations (p < 0.005). Cellular necrosis was more commonly observed in microwave-treated vessels than in control vessels (73% vs. 17%, p < 0.05), but less intraluminal thrombus was seen in vessels exposed to microwave energy (p < 0.05). CONCLUSIONS: Microwave balloon angioplasty is more effective than routine balloon inflations in sealing arterial dissections in this model and appears to be less thrombogenic in these markedly disrupted vessels.

Angiography↗

Genetic modification of the vessel wall. Comparison of surgical and catheter-based techniques for delivery of recombinant adenovirus.

BACKGROUND: Gene transfer can potentially alter vessel wall biology and intervene in the pathogenesis of human disease. Although several methods for vector delivery have been described, systematic comparisons of these methods are unavailable. Therefore, this study compared three catheter-based strategies and a surgical technique to assess efficient and selective gene transfer to the vascular wall. METHODS AND RESULTS: The common carotid arteries and internal jugular veins of New Zealand White rabbits were infected with recombinant adenovirus encoding either firefly luciferase or a nuclear-localizing variant of beta-galactosidase. Delivery of recombinant virus was achieved by one of four methods: (1) instillation within a surgically isolated vessel segment (dwell), (2) a double-balloon catheter, (3) a perforated balloon catheter (Wolinsky), or (4) an angioplasty balloon catheter coated with a hydrophilic adsorbent polymer (Hydrogel). Vessel segments were analyzed 4 days after infection for luciferase and beta-galactosidase activity and for the extent of injury to the vessel wall. Luciferase activity in vessels infected using the double-balloon method was substantially greater than that achieved by catheter-based methods (P < .05). The dwell and double-balloon methods yielded selective expression in intimal cells, whereas arteries infected using perforated or Hydrogel-coated balloon catheters demonstrated expression primarily in medial cells. Tissue injury was most pronounced with the perforated balloon catheter. CONCLUSIONS: Prototype catheters permit relatively efficient direct gene transfer to vascular endothelium; however, delivery methods for targeting the medial cells are inefficient. Modifications are needed to optimize direct gene transfer and minimize tissue injury.

Adenoviridae↗

Hydrogen inhalation for detecting intracardiac left-to-right shunting in adults.

The hydrogen inhalation technique is easily performed and exquisitely sensitive for detecting intracardiac left-to-right shunting. Previous studies of this technique relied heavily on data from infants and children, and the distinction between "normal" and "abnormal" was imprecise and somewhat arbitrary. The present study was done to assess the results of hydrogen inhalation in adults with and without intracardiac left-to-right shunting. In 45 adult subjects (15 men, 30 women, aged 18 to 72 years) (18 without and 27 with intracardiac left-to-right shunting), the elapsed time from hydrogen inhalation to its appearance in the pulmonary artery was measured. The 18 patients without shunting had an appearance time of 12 +/- 3 (mean +/- SD) seconds, and it was > or = 9 seconds in all. In contrast, the 27 subjects with shunting had an appearance time of 1.5 +/- 0.7 second, with only 1 of 27 being > or = 3 seconds. There was no relation between the magnitude of left-to-right shunting and the hydrogen appearance time. Thus, the hydrogen inhalation technique easily and reliably separates adult subjects with and without intracardiac left-to-right shunting, with no overlap between the 2 groups.

Administration, Inhalation↗

Effect of nicotinic acid on plasma glucose concentration in normal individuals.

In order to assess the ability of nicotinic acid to decrease plasma glucose concentration, normal individuals were given continuous four hour infusions of either nicotinic acid (NA), somatostatin (SRIF), NA + SRIF, or 0.9% NaCl (Saline). Plasma non-esterified fatty acid (NEFA) concentration decreased to about one-fourth of the basal value in response to either NA or NA + SRIF, associated with statistically significant decreases in plasma glucose concentration. The ability of NA and NA + SRIF to decrease plasma glucose concentration was seen despite the fact that plasma insulin concentrations also fell significantly during both infusions. Although plasma glucose concentration fell significantly in response to both NA and NA + SRIF, the effect of NA + SRIF was approximately twice as great as that seen with NA alone. The augmented hypoglycaemic effect of NA + SRIF as compared to NA alone was associated with a concomitant fall in plasma glucagon concentration. In contrast, plasma glucose concentration did not change following Saline, and was actually higher than baseline after the infusion of SRIF alone. These results provide evidence that NA can lower plasma glucose concentration in normal volunteers, and suggests that this is mediated by the NA-associated decrease in plasma NEFA concentration.

Blood Glucose↗

Acronyms in angioplasty and restenosis: a summary of recent and ongoing clinical randomized trials.

Trials that pertain to angioplasty and restenosis are a major focus of clinical research in cardiology at present. Investigators, especially those involved in multicenter studies, have become experts in the derivation of acronyms to identify these trials. Meant to capture the spirit of the trial and the attention of those reading the eventual publication of the results, these abbreviations have proliferated in recent times. This article summarizes the major trials with acronym titles, spells out what they stand for, defines what was investigated, and reviews the reported results.

Abbreviations as Topic↗

Peripheral vascular effects of halothane and isoflurane in humans with an artificial heart.

The peripheral vascular effects of isoflurane and halothane were compared in five critically ill patients in whom a Jarvik-7 artificial heart had been implanted. The lungs of all patients were mechanically ventilated in the postoperative period and the patients were monitored with an arterial catheter and with catheters that had been surgically inserted into the right and left atria and into the pulmonary artery. Norepinephrine and epinephrine plasma concentrations were measured using a radioenzymatic assay. The Jarvik-7 settings were modified to render the artificial heart "preload independent" and to maintain cardiac output constant. Each patient was anesthetized twice using halothane and isoflurane at two different MAC levels, 1 and 1.5 (Datex vapour analyzer), with the interval between each anesthetic ranging from 12 to 26 h. Both anesthetics significantly decreased mean arterial pressure (from 100 +/- 11 mmHg to 66 +/- 13 mmHg for halothane and from 102 +/- 17 mmHg to 48 +/- 11 mmHg for isoflurane; mean +/- SD) and systemic vascular resistance index (from 27 +/- 11 Wood units/m2 to 18 +/- 6 Wood units/m2 for halothane and from 30 +/- 6 Wood units/m2 to 13 +/- 3 Wood units/m2 for isoflurane; mean +/- SD), but with isoflurane to a significantly greater extent than with halothane (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of partners in selecting a residency.

To study the influence of medical students' partners (that is, those to whom they are married or engaged, or with whom they are living as "significant others") on students' selections of their residency programs, the authors surveyed fourth-year medical students and their partners at 20 medical schools in 1986. Forty-six percent of 770 eligible couples responded to the questionnaire; data from 314 couples were used in this study. Sixty-five percent of the medical students were men. Eighty-five percent of the partners were employed outside the home. The partner was the most influential person in the students' choice of a residency. Twenty-six percent (81) of the couples mutually made the decision and over 50% (186) tried to satisfy equally both partners' needs. However, the women medical students had less influence over the decision and were more apt to sacrifice their needs for their partners' (p less than .05). The women students were also significantly less satisfied with their role in the decision-making process (p less than .05). Attention to these issues by both medical students and residency programs could help couples deal with the stresses involved in choosing a residency location.

Career Choice↗

Stress in social and family relationships during the medical residency.

A study of stress during residency training involved data analysis of questionnaires completed by 108 residents and fellows in internal medicine. Over 40 percent of the respondents experienced important problems with their spouse or partner. Of these, 72 percent believed that these problems were due to the residency, and 61 percent reported that their spouse or partner agreed with this assessment. Only 21 percent of the residents with relationship problems felt that their hospital work was being affected negatively. A multiple regression analysis showed that 10 variables accounted for 50 percent of the variance in predicting relationship stress. The results suggest that scheduling and structural changes in residencies are necessary in order to reduce stress among residents. Perhaps equally important is the finding that stress can be buffered by family relationships and social contact. The authors conclude that social support systems need to be fostered during the residency.

Adult↗

Fabrication of resorbable microporous intravascular stents for gene therapy applications.

The authors have produced resorbable, microporous endoluminal stents from Poly-L-lactic acid (PLLA)/Poly epsilon-caprolactone (PCL) blends. Both helical and tube stent designs have been obtained by solvent casting and flotation-precipitation fabrication techniques. A range of PLLA/PCL blend ratios and process variables were employed to investigate their influence on mechanical properties, porosity, and degradation rate. Polymer blends with higher PLLA proportions exhibit higher elastic moduli and ultimate tensile strength, and lower elongation, porosity, and degradation rates than do materials with higher PCL content. Stents with suitable mechanical properties for deployment and support of the vessel wall were obtained. Poly(ethylene oxide) was incorporated into these devices using an acid swelling technique, opening the pore structure and improving the hydrophilic character, thereby enabling the uptake of recombinant adenoviral vectors. The 50:50 PLLA/PCL blended stents were impregnated with recombinant adenovirus (AdCMB beta Gal, encoding a nuclear localizing variant of Escherichia coli beta-galactosidase). Cultured CV-1 cells incubated with stents impregnated with the recombinant virus expressed nuclear localized beta-galactosidase activity, confirming that absorbed virus is released from the matrix in an infectious form, with kinetics suggesting that genetically enhanced endovascular devices of this design are feasible.

Adenoviridae↗

Improved bioresorbable microporous intravascular stents for gene therapy.

Drug imbibing microporous stents are under development at a number of centers to enhance healing of the arterial wall after balloon coronary angioplasty procedures. The authors improved the mechanical strength and reservoir properties of a biodegradable microporous stent reported to this Society in 1994. A combined tubular/helical coil stent is readily fabricated by flotation/precipitation and casting/ winding techniques. A two stage solvent swelling technique allows precise adjustment of the surface hydrophilic/hydrophobic balance. These developments permit seven-fold improvement in drug capacity without significantly altering mechanical properties. Stents modified in this manner retain tensile and compressive strength and are suitable for remote deployment. Elution kinetics of these modified stents suggest they are suitable for gene delivery. Successful gene transfer and transmural expression have been demonstrated after implantation of stents impregnated with a recombinant adenovirus carrying a nuclear localizing beta-galactosidase reporter gene into rabbit carotid arteries. These studies suggest that surface modified, bioresorbable polymer stents ultimately may be useful adjunctive devices for gene transfer during percutaneous transluminal revascularization.

Angioplasty, Balloon↗

Bioresorbable microporous stents deliver recombinant adenovirus gene transfer vectors to the arterial wall.

The use of intravascular stents as an adjunct for percutaneous transluminal revascularization is limited by two principal factors, acute thrombosis and neointimal proliferation, resulting in restenosis. To overcome these limitations, we have investigated the potential of microporous bioresorbable polymer stents formed from poly(L-lactic acid) (PLLA)/poly(epsilon-caprolactone) (PCL) blends to function both to provide mechanical support and as reservoirs for local delivery of therapeutic molecules and particles to the vessel wall. Tubular PLLA/PCL stents were fabricated by the flotation-precipitation method, and helical stents were produced by a casting/winding technique. Hybrid structures in which a tubular sheath is deposited on a helical skeleton were also generated. Using a two-stage solvent swelling technique, polyethylene oxide has been incorporated into these stents to improve hydrophilicity and water uptake, and to facilitate the ability of these devices to function as drug carriers. Stents modified in this manner retain axial and radial mechanical strength sufficient to stabilize the vessel wall against elastic recoil caused by vasoconstrictive and mechanical forces. Because of the potential of direct gene transfer into the vessel wall to ameliorate thrombosis and neointimal proliferation, we have investigated the capacity of these polymer stents to function in the delivery of recombinant adenovirus vectors to the vessel wall. In vitro, virus stock was observed to readily absorb into, and elute from these devices in an infectious form, with suitable kinetics. Successful gene transfer and expression has been demonstrated following implantation of polymer stents impregnated with a recombinant adenovirus carrying a nuclear-localizing betaGal reporter gene into rabbit carotid arteries. These studies suggest that surface-modified polymer stents may ultimately be useful adjunctive devices for both mechanical support and gene transfer during percutaneous transluminal revascularization.

Adenoviridae↗